ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Objective:To analyze the effects of biodegradable-polymer sirolimus-eluting stents (BP-SES) and durable polymer sirolimus-eluting stents (DP-SES) implantation on serum endothelin 1 levels and the incidence of coronary restenosis in patients with coronary heart disease (CHD).Methods:A total of 114 patients with CHD admitted to the First People's Hospital of Xianyang in Shaanxi Province from May 2022 to January 2024 were selected. According to the principle of comparable baseline characteristics between groups, patients were divided into two groups by random number table method, with 57 cases in each group. After pretreatment of diseased vessels, DP-SES group underwent implantation of DP-SES with appropriate length and diameter, while BP-SES group underwent implantation of BP-SES with appropriate length and diameter. After implantation, non-compliant balloons were used for in-stent post-dilation. Comparisons of vascular endothelial function, levels of inflammatory factors and hemodynamic indicators before operation and at 6 months between groups were made postoperatively, also, the incidence rates of major adverse cardiovascular events (MACE) and coronary restenosis within 6 months were also compared. Measurement data with normal distribution was expressed as “xˉ±s”, independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:At 6 months after surgery, the levels of endothelin 1 and VEGF were lower in BP-SES group compared to DP-SES group,[(72±5) ng/L vs. (77±7) ng/L, (147±25) ng/L vs. (157±27) ng/L, t=3.76, P<0.001, t=2.16, P=0.033]. The level of nitric oxide was higher in BP-SES group compared to DP-SES group [(79±7) μmol/L vs. (76±8) μmol/L, t=2.46, P<0.001]. At 6 months after surgery, the levels of TNF-α, IL-1 and CRP in DP-SES group were higher than those before surgery, and were all higher compared to BP-SES group[(81±5) ng/L vs. (75±5) ng/L, (159±18) ng/L vs. (151±16) ng/L, (31±4) mg/L vs. (29±3) mg/L, t=6.87, P<0.001, t=2.24, P=0.027, t=2.51, P=0.014]. At 6 months after surgery, the level of whole blood viscosity and plasma viscosity in both group were lower than those before surgery, and the level of Hct in BP-SES group was lower than those before surgery, the differences were statistically significant ( P<0.001), while the differences between groups were not statistically significant( P>0.05). The difference of incidence rates of MACE and coronary restenosis within 6 months between groups before surgery and 6 months after surgery were not statistically significant [7.0%(4/57) vs. 12.3%(7/57), χ2=0.91, P=0.341; 3.7%(2/57) vs. 8.3%(5/57), χ2=0.61, P=0.443]. Conclusion:Both BP-SES implantation and DP-SES implantation could effectively restore coronary blood supply, and are highly safe. However, the former can reduce damage to vascular wall and better improve endothelial function in patients.

Objective:To explore the association of serum levels of 41 serum cytokines and growth factors with the risk of sero-negative rheumatoid arthritis(SNRA)by Mendelian randomization.Methods:Genetic instruments for 41 circulating cytokines and growth factors were determined from a genome-wide association study(GWAS)of 8 293 European participants.Summary statistics for the SNRA were obtained from the Finnish database,including 3 877 SNRA cases and 285 035 controls of European ancestry.All of the inverse variance weighted(IVW),weighted median method(WM)and MR-Egger regression were used for MR analysis,while the IVW method was considered as the main analysis.The sensitivity analysis included a heterogeneity test,horizontal pleiotropic test,and leave-one method test to determine the reliability of the MR results.Results:In the IVW method,TNF-α[OR=1.470,95%CI(1.1331～1.910),P=0.004],IP-10[OR=0.794,95%CI(0.660～0.955),P=0.015]and IL-2rα[OR=0.049,95%CI(0.856～0.999),P=0.049].Sensitivity analysis showed no heterogeneity and horizontal pleiotropy.Conclusion:TNF-α,IP-10 and IL-2rα are causally associated to SNRA.TNF-α increases the risk of SNRA,while IP-10 and IL-2rα reduce the risk of SNRA.

Objective:To analyze the effects of biodegradable-polymer sirolimus-eluting stents (BP-SES) and durable polymer sirolimus-eluting stents (DP-SES) implantation on serum endothelin 1 levels and the incidence of coronary restenosis in patients with coronary heart disease (CHD).Methods:A total of 114 patients with CHD admitted to the First People's Hospital of Xianyang in Shaanxi Province from May 2022 to January 2024 were selected. According to the principle of comparable baseline characteristics between groups, patients were divided into two groups by random number table method, with 57 cases in each group. After pretreatment of diseased vessels, DP-SES group underwent implantation of DP-SES with appropriate length and diameter, while BP-SES group underwent implantation of BP-SES with appropriate length and diameter. After implantation, non-compliant balloons were used for in-stent post-dilation. Comparisons of vascular endothelial function, levels of inflammatory factors and hemodynamic indicators before operation and at 6 months between groups were made postoperatively, also, the incidence rates of major adverse cardiovascular events (MACE) and coronary restenosis within 6 months were also compared. Measurement data with normal distribution was expressed as “xˉ±s”, independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:At 6 months after surgery, the levels of endothelin 1 and VEGF were lower in BP-SES group compared to DP-SES group,[(72±5) ng/L vs. (77±7) ng/L, (147±25) ng/L vs. (157±27) ng/L, t=3.76, P<0.001, t=2.16, P=0.033]. The level of nitric oxide was higher in BP-SES group compared to DP-SES group [(79±7) μmol/L vs. (76±8) μmol/L, t=2.46, P<0.001]. At 6 months after surgery, the levels of TNF-α, IL-1 and CRP in DP-SES group were higher than those before surgery, and were all higher compared to BP-SES group[(81±5) ng/L vs. (75±5) ng/L, (159±18) ng/L vs. (151±16) ng/L, (31±4) mg/L vs. (29±3) mg/L, t=6.87, P<0.001, t=2.24, P=0.027, t=2.51, P=0.014]. At 6 months after surgery, the level of whole blood viscosity and plasma viscosity in both group were lower than those before surgery, and the level of Hct in BP-SES group was lower than those before surgery, the differences were statistically significant ( P<0.001), while the differences between groups were not statistically significant( P>0.05). The difference of incidence rates of MACE and coronary restenosis within 6 months between groups before surgery and 6 months after surgery were not statistically significant [7.0%(4/57) vs. 12.3%(7/57), χ2=0.91, P=0.341; 3.7%(2/57) vs. 8.3%(5/57), χ2=0.61, P=0.443]. Conclusion:Both BP-SES implantation and DP-SES implantation could effectively restore coronary blood supply, and are highly safe. However, the former can reduce damage to vascular wall and better improve endothelial function in patients.

Objective:To explore the association of serum levels of 41 serum cytokines and growth factors with the risk of sero-negative rheumatoid arthritis(SNRA)by Mendelian randomization.Methods:Genetic instruments for 41 circulating cytokines and growth factors were determined from a genome-wide association study(GWAS)of 8 293 European participants.Summary statistics for the SNRA were obtained from the Finnish database,including 3 877 SNRA cases and 285 035 controls of European ancestry.All of the inverse variance weighted(IVW),weighted median method(WM)and MR-Egger regression were used for MR analysis,while the IVW method was considered as the main analysis.The sensitivity analysis included a heterogeneity test,horizontal pleiotropic test,and leave-one method test to determine the reliability of the MR results.Results:In the IVW method,TNF-α[OR=1.470,95%CI(1.1331～1.910),P=0.004],IP-10[OR=0.794,95%CI(0.660～0.955),P=0.015]and IL-2rα[OR=0.049,95%CI(0.856～0.999),P=0.049].Sensitivity analysis showed no heterogeneity and horizontal pleiotropy.Conclusion:TNF-α,IP-10 and IL-2rα are causally associated to SNRA.TNF-α increases the risk of SNRA,while IP-10 and IL-2rα reduce the risk of SNRA.

Objective:To investigate the utilization of Internet plus nursing service and its influencing factors.Methods:From October 2018 to January 2019, 247 patients registered on the Internet plus nursing service platform were randomly surveyed to understand the status quo of Internet plus nursing service. The influencing factors were analyzed based on the Anderson health service model.Results:Among the 247 patients who received Internet plus nursing, 74.5%(184 cases) were women. The average age was 37 years(20-81 years). The median number of times of nursing service received by the patients was 2 times. Infusion was the most accepted nursing service on the platform. Patients who are older, do not have basic medical insurance, the source of routine care is not a Class A tertiary hospital, and do not have chronic diseases used the Internet platform to receive nursing services more frequently.Conclusions:Internet plus nursing service has been initially recognized by patients. The predisposing factor affecting the tendency of individuals to continue using Internet plus nursing services is age, enabling factors are health insurance status and regular nursing sources, and the need factor is chronic disease.

Objective To investigate the effect of PM2.5 airborne particulate matter with a mean diameter of less than 2.5μm exposure on autophagy and explore the links between autophagy and apoptosis in human lung cancer cells(A549). Methods A549 cells were exposed to 100μg/mL PM2.5 with or without 3-MA(autophagy inhibitor)for various periods of 0、2、4、12 or 24 hrs. Autophagy in A549 cells was assessed by determining the lev-el of LC3(a known autophagy marker)using confocal microscopy. The level of microtubule-associated protein 1 light chain 3(LC3) Ⅱ conversion and Bax (a pro-apoptotic protein) was detected by western blotting. Results The expression of LC3 and the ratio of LC3-II/LC3-I in A549 cells was significantly increased and Bax was signifi-cantly decreased following exposure to PM2.5100 μg/mL for 24 h in a time-dependent manner(P < 0.05). After treated with 100 μg/mL PM2.5,the formation of LC3 in A549 cells as evidenced by the intensity of intracellular fluorescence was significantly increased ,and autophageosomes were observed around nucleus in A549 cells. Fur-thermore blockage of autophagy by 3-MA led to a significant increase in the pro-apoptotic protein Bax. Conclu-sion PM2.5 exposure induces autophagy which may protect against apoptosis induced by PM2.5 in A549 cells.

Lots of evidence show a correlation between air pollution and chronic respiratory diseases, of which the effect of particulate matter is the most concerned.It is the current research hotspot that respiratory diseases in both children and adults are closely related with atmospheric pollution levels.The influence mechanisms of atmos-pheric pollution on respiratory diseases include oxidative stress, inflammation, genetic damage, etc.This paper made a review of the latest advances s on the pathogenesis of chronic respiratory diseases caused by atmospheric particulates PM2.5 .